Yagita M
Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
J UOEH. 1988 Jun 1;10(2):189-201. doi: 10.7888/juoeh.10.189.
The effect of histamine H2-antagonists on serum gastrin concentration and histamine-stimulated gastric acid secretion was studied in gastric lumen-perfused rats in which changes in the intragastric pH were limited by using 2.5 mM propionate-succinate buffer as perfusate. The gastric acid secretion was measured by the titration of the acidity of gastric juice with 0.05 N NaOH. The serum gastrin levels were determined in the blood that was obtained simultaneously with gastric juice by radioimmunoassay. The gastric acid secretion was inhibited by these histamine H2-antagonists--cimetidine, famotidine, ranitidine and TZU-0460 administered intravenously. Within the dose-response range of the inhibition of gastric acid secretion, cimetidine and ranitidine increased significantly the serum gastrin levels, but famotidine and TZU-0460 did not. The doses of famotidine and TZU-0460 which were used to increase the serum gastrin levels were found to be higher than those for the maximal inhibition of gastric acid secretion. They also presented a dose-response curve to the serum gastrin levels similar to cimetidine and ranitidine. The findings suggest that histamine H2-antagonists have a potency to increase serum gastrin levels to that of the inhibition of gastric acid secretion.
在胃腔灌注大鼠中研究了组胺H2拮抗剂对血清胃泌素浓度和组胺刺激的胃酸分泌的影响，其中使用2.5 mM丙酸盐 - 琥珀酸盐缓冲液作为灌注液来限制胃内pH的变化。通过用0.05 N NaOH滴定胃液酸度来测量胃酸分泌。通过放射免疫测定法在与胃液同时采集的血液中测定血清胃泌素水平。静脉注射西咪替丁、法莫替丁、雷尼替丁和TZU - 0460这些组胺H2拮抗剂可抑制胃酸分泌。在胃酸分泌抑制的剂量反应范围内，西咪替丁和雷尼替丁显著提高血清胃泌素水平，但法莫替丁和TZU - 0460则不然。发现用于提高血清胃泌素水平的法莫替丁和TZU - 0460的剂量高于最大抑制胃酸分泌的剂量。它们对血清胃泌素水平也呈现出与西咪替丁和雷尼替丁相似的剂量反应曲线。这些发现表明，组胺H2拮抗剂具有在抑制胃酸分泌的同时提高血清胃泌素水平的能力。
